Transcription factor AP-2α activates RNA polymerase III-directed transcription and tumor cell proliferation by controlling expression of c-MYC and p53.

Content Provider	Europe PMC
Author	Wang, Juan Chen, Qiyue Peng, Feixia Zhao, Shasha Zhang, Cheng Song, Xiaoye Yu, Deen Wu, Zhongyu Du, Jiannan Ni, Hongwei Deng, Huan Deng, Wensheng
Copyright Year	2023
Abstract	Deregulation of transcription factor AP2 alpha (TFAP2A) and RNA polymerase III (Pol III) products is associated with tumorigenesis. However, the mechanism underlying this event is not fully understood and the connection between TFAP2A and Pol III–directed transcription has not been investigated. Here, we report that TFAP2A functions as a positive factor in the regulation of Pol III–directed transcription and cell proliferation. We found TFAP2A is also required for the activation of Pol III transcription induced by the silencing of filamin A, a well-known cytoskeletal protein and an inhibitor in Pol III–dependent transcription identified previously. Using a chromatin immunoprecipitation technique, we showed TFAP2A positively modulates the assembly of Pol III transcription machinery factors at Pol III–transcribed gene loci. We found TFAP2A can activate the expression of Pol III transcription-related factors, including BRF1, GTF3C2, and c-MYC. Furthermore, we demonstrate TFAP2A enhances expression of MDM2, a negative regulator of tumor suppressor p53, and also inhibits p53 expression. Finally, we found MDM2 overexpression can rescue the inhibition of Pol III–directed transcription and cell proliferation caused by TFAP2A silencing. In summary, we identified that TFAP2A can activate Pol III–directed transcription by controlling multiple pathways, including general transcription factors, c-MYC and MDM2/p53. The findings from this study provide novel insights into the regulatory mechanisms of Pol III–dependent transcription and cancer cell proliferation.
ISSN	00219258
Volume Number	299
PubMed Central reference number	PMC9999235
Issue Number	3
PubMed reference number	36707053
Journal	The Journal of Biological Chemistry [J. Biol. Chem]
e-ISSN	1083351X
DOI	10.1016/j.jbc.2023.102945
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2023-01-25
Access Restriction	Open
Rights License	This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). © 2023 The Authors
Subject Keyword	RNA polymerase III gene transcription TFAP2A cell proliferation signaling pathways ChIP, chromatin immunoprecipitation FLNA, Filamin A Pol III, RNA polymerase III RT-qPCR, reverse transcription–quantitative polymerase chain reaction TFAP2A, transcription factor AP2 alpha
Content Type	Text
Resource Type	Article
Subject	Cell Biology Molecular Biology Biochemistry